Distance geometry is a method of conformational analysis that plays a central role in the determination of protein and nucleic acid structure in solution from a wide variety of experimental data. The purpose of this research is to demonstrate the applicability of distance geometry to two other important classes of conformational problems in structural molecular biology. The first of these is the prediction of protein conformation from the crystal and/or NMR structures of homologous proteins by means of sequence alignments. The method will first be demonstrated and evaluated by predicting the structure of the flavodoxin from E. coli in parallel with the determination of its crystal structure. It will then be used to predict the structures of several interesting new and mutant proteins, including various members of the cyclophilin cis-trans isomerases and the variable domains of immunoglobulins. The second class of problems is the prediction of new ligands that bind to specific sites on proteins of known structure. The methods used here will first be developed and evaluated on the well-known dihydrofolate reductase system, and then used to search for new inhibitors for the cyclophilins. Finally, the possibility of using these methods together with the known structures of Fab/antigen complexes to predict the cross-reactivity of immunoglobulin/hapten pairs will be explored.